Functional near infrared spectroscopy (fNIRS) is an emerging non-invasive imaging technique to assess the brain function. The technique is non-invasive and portable and therefore applicable in studies of children and toddlers especially those with neurodevelopmental disorders. fNIRS measurements are based on the local changes in cerebral hemodynamic levels (oxy-hemoglobin and deoxy-hemoglobin) associated with brain activity. Due to the low optical absorption of biological tissues at NIR wavelengths (700-900 nm), NIR light can penetrate deep enough to probe the cortical regions up to 1-3 cm deep. The NIR absorption spectrum of the tissue is sensitive to changes in the concentration of major tissue chromophores, such as hemoglobin. Therefore, measurements of temporal variations of backscattered light can capture functionally evoked changes in cortex to assess the brain function. Two general tracks of research involving fNIRS in the brain are currently being pursued in our lab: developmental trajectories of cognitive abilities, and the comparison of fNIRS to cognitive tasks that have been evaluated using fMRI. Previous studies that we have conducted examined measures of prefrontal cortical activation using fNIRS as they relate to developmental level in toddlers. We have continued this work in 2018 through a series of projects and collaborations. First, as part of a previous collaboration with Dr. Audrey Thurm (NIMH), we have worked on a project where 24-month-old toddlers listened to speech sounds or watched gesture production while recording fNIRS in the prefrontal cortex. Over the past year, the data from this project was analyzed and manuscripts are currently under review and published. As a continuation of this work, we have begun another project which will examine the developmental trajectory of the mirror neuron network in infants (IRB # 18-CH-N001). The mirror neuron network (MNN) is associated with the development of sophisticated social behaviors that emerge in typical human infants (e.g., complex imitation, decoding emotional states). Modeling MNN development will create a sensitive measure of deviations in social communication development before clinical behavioral deficits can be detected. MNN activation has already been associated with Mu suppression using EEG. Using EEG (with high temporal resolution) in conjunction with fNIRS will provide more precise spatial resolution of neural activity based on hemodynamic activation to investigate the MNN. In the pilot study, we have begun recruiting healthy adults to see whether MNN activation can be elicited using a motor observation and execution paradigm and recorded through an EEG/fNIRS system simultaneously. We will examine the synchronicity of these signals as they relate to social communication and cognitive functioning in typically developing adults. We have successfully collected pilot data in 6 subjects with a goal of 40 adult pilot subjects. After piloting has been completed, we will recruit typically developing infants (9-12 months) (n=60) and infants at-risk for developmental delays (n=60) to collect their simultaneous fNIRS/EEG signals during the motor observation and execution paradigm. At-risk infants will be brought in again at 24 months of age to evaluate any deviations in their social communicative development. Their developmental status will be examined in relation to their initial neural data to see if MNN activation at this age can predict developmental outcomes. We aim to begin recruiting infants for this phase of the project in January 2019. Through a collaboration with Dr. Andrea Gropman at Childrens National Medical Center, we are examining developmental deficits in children with Urea Cycle Disorders (UCD). UCDs are a set of rare genetic disorders caused by the loss of enzymatic activities (such as transcarbamylase deficiency (OTCD)) that mediate the transfer of nitrogen from ammonia to urea. UCD often results in life-threatening hyperammonemia resulting in a broad range of neurological impairments in working memory and executive function. Dr. Gropman, world renowned expert on UCD, found that patients with OTCD showed impairments in frontal lobe processing through their performance on a working memory task compared to a control group using fMRI. We are replicating this work using fNIRS. We have recorded hemodynamic activity from prefrontal cortex from 26 children and adults (control and with UCD) while performing n-back and color and word Stroop tasks. Data collection for this project is ongoing, with a goal of 40 subjects. We will continue data collection and analysis for this project over the next year. Lastly, as part of our ongoing fNIRS calibration protocol (IRB #10-CH-0198), a paper was published examining working memory in typically developing adults revealing that individual differences in learning style can affect the lateralization of prefrontal cortex during the execution of working memory task. Other studies under this protocol were also developed over the past year. One study implemented a moral judgment (MJ) task that is based on a series of questions which examines personal (emotionally salient) versus impersonal (less emotional and more logical) dilemmas. We hypothesized that the brain exhibits distinguishable hemodynamic patterns for each dilemma and investigated the correlation between these patterns and psychopathic traits as measured by Psychopathic Personality Inventory-Revised Content Scale (PPI-R-CS, self-reported). We analyzed the fNIRS data using a non-linear classification method, cubic SVM. We found brain activity is significantly different during personal and impersonal dilemmas, with the mean accuracy of 85%. Using mixed effect models, we found left dorsolateral PFC is highly activated when subjects making non-utilitarian decision (benefiting the majority group rather than a small number of people) for impersonal moral dilemmas. Finally, our results using Canonical Correlation Analysis (CCA) showed significant correlation between PFC activation and psychopathic traits (PPI-R-CS). Specifically, coldheartedness and carefree non-planfulness are highly correlated with PFC activation during personal MJ, while Machiavellian egocentricity, rebellious nonconformity, coldheartedness, and carefree non-planfulness are the core traits that exhibit the same dynamics with PFC activation during impersonal (more logical) MJ. Activation in ventromedial prefrontal cortex (vmPFC) and left lateral PFC were positively correlated with PPI-R-CS traits during personal MJ, and the right vmPFC and right lateral PFC during impersonal MJ. Two papers from this project are currently under review. Additionally, we conducted a study to examine neural activation during a inhibition task, the go/no-go task. The go/no-go task is an executive function task which activates prefrontal cortical areas, as previously established through fMRI research. In the present study, the go/no-go task was administered to 44 typically developing adults while fNIRS and heart rate was recorded. The goal of this study was to establish the utility of fNIRS in evaluating prefrontal activation during a behavior inhibition task. We found that fNIRS distinguished differences between baseline and the go/no-go task, and could be a suitable alternative to fMRI in the evaluation of behavior inhibition. Data are being further analyzed to see if fNIRS measurements are related to individuals level of task performance, or to more general measures of day-to-day behavior inhibition abilities (e.g., self-report). Analysis is ongoing, with the goal of submitting a manuscript by December 2018.